Abstract (Overall) The overall goal of this application is to continue and expand operation of the National Swine Resource and Research Center (NSRRC). The NSRRC is in its 14th year of operation and it has developed the infrastructure needed to assist swine-based research across multiple disciplines, including xenotransplantation. The NSRRC has developed new models of human disease by genetic engineering, it has recruited models created by others, and it has distributed expertise, cells, tissues, organs and pigs to investigators throughout the United States. Since genetic engineering of pigs requires specialized facilities and expertise, the NSRRC provides invaluable services to the research community by using the latest in gene editing technology to create new genetically-engineered swine models. The NSRRC also provides training and education by interacting with individuals, publishing manuscripts and sponsoring workshops and meetings that promote the use of pigs for studying human diseases. The NSRRC has a state-of-the-art building with high biosecurity to house animals free of specific pathogens. The Specific Aims for the upcoming grant period are as follows: 1. To operate the National Swine Research and Resource Center. Functions of the NSRRC will continue to include: a) importation of existing swine models of human health and disease; b) rederivation of pigs to eliminate specific pathogens, and health monitoring to assure maintenance of a specific pathogen-free status; c) cryopreservation and storage of gametes, embryos, and somatic cells to prevent future loss of valuable models; d) distribution of expertise, reagents, cells, tissues, organs, and pathogen-free pigs; and e) use state of the art technology for the creation of new genetically-engineered pigs needed by the biomedical research community. Rigorous quality control will ensure that only high quality genetics are distributed. The NSRRC will also serve as a site for training and educational activities related to research employing swine models. 2. To perform innovative research that will benefit the NSRRC and the biomedical research community. Applied research projects are aimed at improving: a) the cryopreservation of pig reproductive cells and tissues, b) methods for the production of genetically-engineered pigs, c) state-of-the-art testing methods for swine health surveillance, and d) right-size the pig for greater adoption of pig models.